ObjectiveTo observe the clinical features of late-onset cone dystrophy (LOCD). MethodsEleven patients (15 eyes) of LOCD were enrolled in this study. The patients included 7 males and 4 females. The age was ranged from 50 to 79 years, with a mean age of 60.2 years. There was no obvious photophobia and hemeralopia. The visual acuity was less than or equal to 0.05 in 4 eyes, 0.06-0.2 in 5 eyes, 0.3-1.0 in 6 eyes. Visual acuity, slit lamp microscope, indirect ophthalmoscopy, flash electroretinogram (FERG) and multifocal electroretinograms (mfERG) were examined for all patients, fundus fluorescein angiography (FFA) for 11 eyes, optical coherence tomography (OCT) and chromoptometry for 6 eyes. ResultsThere were 6 eyes with red/green color blindness, 2 eyes with color weakness. Normal fundus was found in 11 eyes, while derangement of macular pigment epithelial in 4 eyes. FFA results showed that there were 5 eyes with normal fundus, 4 eyes with blocked fluorescent spots, 2 eyes with oval macular atrophy. FERG results showed that in cone response, the amplitude was lower in 6 eyes (including mild decrease in 4 eyes, moderate decrease in 1 eye and severe decrease in 1 eye); both in cone and rod response, the amplitude were lower in 9 eyes. mfERG results showed that central part of the cone (less than 7 degree from the center) was damaged in 5 eyes, both central and peripheral part (outside of 7 degree) of the cone were damaged in 10 eyes. OCT results showed that pigment derangement in 3 eyes, fovea was normal in 8 eyes, thinned in 5 eyes (foveal thickness was 83-111 μm). ConclusionsThe fundus manifestations of LOCD patients are variable, from normal fundus to oval macular atrophy. FERG is abnormal, which mainly in cone response at early stage and both in cone and rod response at late stage. Central part and (or) peripheral part of the cone are abnormal by mfERG.
Objective To investigate the clinical manifestations and gene mutation of a pedigree with retinal lattice degeneration and granular corneal dystrophy (GCD) type 2. Methods Ten members in 3 generations of a pedigree with retinal lattice degeneration and GCD2 were included in the study, including 6 patients (3 males and 3 females) and 4 healthy family members. All members underwent visual acuity, slit lamp microscope, three-mirror lens, fundus color photography, optical coherence tomography, and corneal endothelial cells counting. Genomic DNA was extracted from peripheral venous blood (2 ml) from all the subjects and their spouses, who had no related inherited diseases. The next generation sequencing method was used to detect the mutation sites of transforming growth factor β (TGFBI), and all results underwent Sanger verification. Results Among the 12 eyes of 6 patients, the visual acuity was FC/20 cm-1.0. In the superficial central corneal stroma, snowflake-like deposits were observed in three cases (6 eyes), and a small amount of granular deposits were observed in three cases (6 eyes). Corneal endothelial cell counts were normal. Retinal lattice degeneration were observed in 3 cases, 6 eyes (including 3 cases of rhegmatogenous retinal detachment in 4 eyes); retinal thinning without obvious lattice degeneration in 4 eyes of 2 patients. Nystagmus in 1 patient and fundus examination showed no significant abnormalities. DNA sequencing results showed that the proband and 4 patients had missense mutation of TGFBI gene in exon 4 c.371G＞ A, the mutation site corresponding to the amino acid change encoded by TGFBI gene No. 124 Amino acids, from arginine to histidine (p.R124H). Patients with this mutation have varying degrees of clinical phenotype. Conclusions The mutation of c.701G＞ A (p.R124H) in TGFBI gene is the causative gene of GCD in this pedigree. The patients with this mutation have different clinical phenotypes.
ObjectiveTo observe the safety of 2-port non-vitrectomized subretinal injection (SRI) for the treatment of Bietti crystalline dystrophy (BCD). MethodsA exploratory clinical study. From February to May 2023, 6 BCD patients with 6 eyes who were confirmed by examination in Xiamen Eye Center of Xiamen University and were treated with SRI adeno-associated virus vector transgenic drugs were included in the study. Among them, 2 males had 2 eyes and 4 females had 4 eyes. Age were 34-60 years old. The study eye underwent adeno associated virus gene therapy via 2-port non-vitrectomized SRI. Two scleral ports were created using 25G vitrectomy trocar to place the light pipe and injection cannula. Anterior chamber paracentesis was performed to lower intraocular pressure. Under the silicone oil infusion mode of the vitrectomy machine, a 38G injection cannula penetrated the retina to reach the subretinal space. The injection speed was controlled by the foot pedal of the vitrectomy machine, and the drug was slowly injected into the subretinal space to create a subretinal bleb. if intra-ocular pressure assessed by finger palpation was high at the end of injection, drainage of the aqueous humor can be made by compressing the cornea incision until the intraocular pressure was normal. Patients were followed for 9-12 months and be examined using the same equipment and methods as before. ResultsRetinal pigment epithelium and choroidal atrophy were observed in all 6 eyes of 6 patients were graded as stage Ⅲ by the fundus examination revealing atrophy of retinal pigmented epithelium and choroid, with or without yellow-white crystals and/or complex lipid. The range were operation time 9-14 minutes. No vitreous prolapse, retinal hemorrhage, or retinal tear was observed during surgery. After 24 hours, optical coherence tomogrophy examination showed absorption of subretinal fluid and retinal reattachment. None of the six patients showed corneal keratic precipitates, anterior chamber cells, vitreous cells, inflammation, high intraocular pressure, or retinal tear within the 9-month follow-up. ConclusionSubretinal injection without vitrectomy using two ports is a safe and feasible alternative for adult gene therapy, and it shortens the surgical time.